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Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats

Authors
Hofbauer B.Saluja A.K.Lerch M.M.Bhagat L.Bhatia M.Lee H.S.Frossard J.L.Adler G.Steer M.L.
Issue Date
1998
Publisher
American Physiological Society
Keywords
Cathepsin B; Immunolocalization; Pancreas; Subcellular fractionation; Trypsin; Trypsinogen activation peptide
Citation
American Journal of Physiology - Gastrointestinal and Liver Physiology, v.275, no.2 38-2, pp.G352 - G362
Indexed
SCOPUS
Journal Title
American Journal of Physiology - Gastrointestinal and Liver Physiology
Volume
275
Number
2 38-2
Start Page
G352
End Page
G362
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/25025
DOI
10.1152/ajpgi.1998.275.2.g352
ISSN
0193-1857
Abstract
Supramaximal stimulation of the pancreas with the CCK analog caerulein causes acute edematous pancreatitis. In this model, active trypsin can be detected in the pancreas shortly after the start of supramaximal stimulation. Incubation of pancreatic acini in vitro with a supramaximally stimulating caerulein concentration also results in rapid activation of trypsinogen. In the current study, we have used the techniques of subcellular fractionation and both light and electron microscopy immunolocalization to identify the site of trypsinogen activation and the subsequent fate of trypsin during caerulein-induced pancreatitis. We report that trypsin activity and trypsinogen-activation peptide (TAP), which is released on activation of trypsinogen, are first detectable in a heavy subcellular fraction. This fraction is enriched in digestive enzyme zymogens and lysosomal hydrolases. Subsequent to trypsinogen activation, both trypsin activity and TAP move to a soluble compartment. Immunolocalization studies indicate that trypsinogen activation occurs in cytoplasmic vacuoles that contain the lysosomal hydrolase cathepsin B. These observations suggest that, during the early stages of pancreatitis, trypsinogen is activated in subcellular organelles containing colocalized digestive enzyme zymogens and lysosomal hydrolases and that, subsequent to its activation, trypsin is released into the cytosol.
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안암병원 (Department of Gastroenterology and Hepatology, Anam Hospital)
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